Fig. 6: Using JAKi to inhibit SASP secretion from senescent stem cells rescues the therapeutic effect of lymphatic proliferation on osteolysis in aged mice.

a Model of co-culture involving BMSCs treated with adipogenic differentiation medium and LECs. Mouse bone marrow-derived stem cells were seeded in the upper insert at a density of 5 × 10⁴ cells/well, while the lower layer of LECs was evenly plated at a density of 1 × 10⁵ cells/well. b IF images of Anti-LYVE1 antibody and Anti-PROX1 antibody demonstrate that upper-layer adipogenically differentiated BMSCs inhibit the proliferation of lower-layer LECs. However, this inhibitory effect can be reversed by using JAK inhibitor on the upper insert. Scale bar, 50 µm. c Micro-CT images illustrate cranial bone resorption from both superior and inferior perspectives after continuous TAP treatment for 14 days, along with subcutaneous injection of recombinant VEGF-C, oral administration of JAK inhibitor, or their combination. d TRAP staining was performed on mouse cranial bones following TAP treatment, combined with subcutaneous injection of recombinant VEGF-C, oral administration of JAK inhibitor, or their combination. Scale bars: 100 μm. e H&E staining was performed on mouse cranial bones following TAP treatment, combined with subcutaneous injection of recombinant VEGF-C, oral administration of JAK inhibitor, or their combination. Scale bars: 100 μm. f IF staining for DAPI with LYVE1 (green) and PROX1 (red). Scale bars, 100 μm. g Micro-CT images illustrating cranial bone resorption in aging mice from both superior and inferior perspectives following TAP treatment, combined with subcutaneous injection of recombinant VEGF-C, oral administration of JAK inhibitor, or their combination. h Quantification of TRAP-stained areas in calvarial bone sections (n = 6). i Quantification of inflammatory infiltrating cells in calvarial bone sections (n = 6). j, k The corresponding quantitative data for LYVE1 (green) and PROX1 (red) expressions in cranial bones on day 14 after combined TAP treatment, subcutaneous injection of recombinant VEGF-C, oral administration of JAK inhibitor, or their combination (n = 6). Data are shown as means ± SD. Significance was assessed through one-way ANOVA.